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The effect of metabolic inhibitors, piretanide, somatostatin and insulin on fluid secretion by in vitro fetal lungs from guinea pigs (Cavia porcellus)

University of British Columbia

This study introduced the isolated lungs of fetal guinea pigs as a new preparation for the investigation of prenatal lung physiology. It established their basic properties by the use of metabolic inhibitors and the CI- transport inhibitor, piretanide. In addition, the effects of two naturally occurring peptides, somatostatin and insulin were investigated. It also extended studies to a species which has received no investigation by modern methods. The fetal lungs of fetuses from near term guinea pigs (54 to 67 days gestation) were used. The total volume of lung fluid was measured during three hours by dye-dilution of Blue Dextran 2000. In the second hour the lungs were exposed to one of the substances under investigation. Untreated fetal lungs continued to secrete in vitro for three hours. The average rate of secretion during the first hour (2.31 ± 0.17 ml/Kg per h; n=104) is comparable to secretion rates reported in chronically catheterized fetal lambs. The combined data of the control groups showed a steady increase in lung fluid volume throughout the three hours of experiment. Sodium iodoacetate (10⁻³M and 10⁻⁴M), an inhibitor of the glycolytic pathway, reduced lung fluid secretion. Sodium fluoride, an alternative inhibitor of glycolysis, also reduced secretion. The possible importance of the aerobic metabolic pathways was tested by the use of NaCN (10⁻³M). The results were more variable than those from the glycolytic inhibitors, and suggest that NaCN slightly reduces the secretion rate. Sodium azide was tested as an alternative inhibitor of the aerobic metabolic pathway with similar results to those from NaCN, confirming that the oxidative pathway has some influence on lung secretion, although it does not appear as important as the glycolytic system. Dinitrophenol was tested as an alternative inhibitor of oxidative processes. The results suggest that dinitrophenol not only abolishes secretion but also produces reabsorption. Piretanide, a loop diuretic capable of inhibiting Na⁺/K⁺/CI⁻ co-transport, reduced lung fluid secretion rates at both 10⁻⁷M and 10⁻⁸M. Somatostatin, a natural inhibitor of Cl⁻ secretion in some tissues, reduced secretion at both 10⁻⁵M and 10⁻⁶M (no significant effect at 10⁻⁷M). Insulin is known to influence the maturity of fetal lungs, and to stimulate Na⁺ transport in some tissues; Na⁺ transport is probably involved in reabsorption. The results showed that insulin at 10⁻⁶- 10⁻⁷M reduced secretion by the isolated lung. This study suggests that the in vitro fetal lung could be a useful tool for future study.

Text

2010-08-23

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http://hdl.handle.net/2429/27633

Zoology

University of British Columbia

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